1. Field of the Invention
This invention pertains to methods and apparatus for treating tissue of a patient's heart. More particularly, this invention pertains to methods and apparatus for treating a region of heart tissue with therapeutic agents for treatment of microvascular obstructions. Also, the present invention pertains to treating an infarcted region of cardiac tissue.
2. Description of the Prior Art
The heart includes numerous coronary arteries for supplying oxygenated blood to the tissue of the heart. Occasionally, one or more of these coronary arteries may become fully or partially occluded. Upon such occurrence, the region of heart tissue served by the occluded vessel is deprived of oxygen.
If the occlusion occurs in a large vessel (e.g., a proximal portion of the left anterior descending artery, LAD), a large portion of the heart (e.g., the left side of the heart) is affected. If the occlusion occurs in a smaller vessel (e.g., a distal portion of the LAD or a branch of the LAD), a smaller region of heart tissue is affected.
The occlusion may progress to such a degree that the tissue in the region may become ischemic. Such ischemic tissue may revive after being re-supplied with an adequate flow of oxygenated blood. If left untreated and inadequately supplied with oxygenated blood, such tissue can become necrotic. Necrotic or infarcted tissue is a permanent injury to heart tissue. Such infarcted areas do not meaningfully participate in the pumping function of the heart. If the region of infarcted tissue is large enough, the patient may develop heart failure or die.
A patient with a coronary artery occlusion may have symptoms (such as chest pain) upon exertion. Location of an occlusion can be determined by an angiogram procedure. In such a procedure, a radiopaque dye is injected into the coronary arteries. The heart is inspected under fluoroscopy and the location of the occlusion is noted.
An occlusion can be treated in a number of different ways. Interventional treatments include surgery and percutaneous treatments. In surgery, a harvested blood vessel is attached to the occluded coronary artery distal to the occlusion. Percutaneous procedures include, among others, balloon angioplasty and stenting. In angioplasty, a balloon is placed in the artery in the region of the occlusion. Expansion of the balloon opens the occlusion. Stenting is similar differing in that a stent (e.g., a metal cage) is left in place at the site of the occlusion.
Intervention can greatly improve a patient's condition. However, a significant number of patient's continue to experience symptoms consistent with occlusion after such intervention. One cause of such persistent symptoms is believed to be microvascular obstruction. In such patients, the microvasculature of the heart (e.g., the arterioles and the capillaries at which the oxygen-carbon dioxide exchange occurs) is occluded with microscopic obstructions.
Microvascular obstruction is common in post-myocardial infarction patients. “In fully 25% of patients in whom arterial obstruction is successfully relieved, little to no additional myocardial perfusion results. These patients . . . exhibit a substantial increase in overall morbidity and mortality.” Alfayoumi, F., et al., “The No-Reflow Phenomenon: Epidemiology, Pathophysiology, and Therapeutic Approach”, Reviews in CV Medicine, Vol 6, No 2, p 72-83 (2005). The frequency of microvascular obstruction is up to 44% in patients undergoing primary interventions for acute myocardial infarction. Marzilli M., et al., “Primary Coronary Angioplasty in Acute Myocardial Infarction: Clinical Correlates of the ‘No Reflow’ Phenomenon”, International J. of Cardiology, Vol. 65 (Suppl. 1) pp. S23-S28 (1998). Assali, A R., et al., “Intracoronary Adenosine Administered During Percutaneous Intervention in Acute Myocardial Infarction and Reduction in the Incidence of ‘No Reflow’ Phenomenon”, Catheter Cardiovasc Interv, Vol. 51, No. 1, pp. 27-31 (2000).
Microvascular obstruction is associated with very serious negative prognosis with profound clinical consequences including heart failure. Persistent microvascular obstruction is a more powerful predictor of survival than infarct size and a high risk factor for late ventricular remodeling. Kramer, C. M., “The Prognostic Significance of Microvascular Obstruction after Myocardial Infarction as Defined by Cardiovascular Magnetic Resonance”, European Heart Journal, Vol. 26, pp. 532-533 (2005). “ . . . [T]he risk of subsequent major adverse events [is] as much as 10 times higher in the no-reflow population than in historical control patients.” Resnic, F S., et al., “No-Reflow is an Independent Predictor of Death and Myocardial Infarction after Percutaneous Intervention”, American Heart J, Vol. 145, No. 1, pp. 42-46 (2003).
Currently, treatment options for microvascular obstruction are limited and of generally inadequate effectiveness. Such treatments include systemic infusion of vasodilators, anti-platelet, and anti-thrombin agents. These treatments have produced disappointing results. Treatment options for ischemia are also limited. These include regional blood flow augmentation and treatment for enhanced function. Such treatments include delivery of angiogenic agents to encourage new vessel growth and cell delivery to improve function.
More recently developed treatments for microvascular obstruction include intracoronary injection of therapeutic agents to treat the microvascular occlusion. These agents include vasodilators (adenosine, verapamil, nitroprusside) and anti-platelet agents (IIb/IIIa). These treatments show some promise. However, these treatments are supported by only very limited studies. Also, such treatments have the potential for systemic toxicity.
It is an object of the present invention to provide a treatment for microvascular obstruction in a region of a patient's heart and treatment of regional myocardial ischemia.